tbuckley/cabot-search huggingface dataset:
High- Versus Low-Dose Exercise Therapy for Knee Osteoarthritis
Authors: Tom Arild Torstensen, Håvard Østerås, Riccardo LoMartire, Georg Mørtvedt Rugelbak, Wilhelmus Johannes Andreas Grooten, Björn Olov Äng
Journal: Annals of Internal Medicine (2023)

The benefits of exercise in patients with knee osteoarthritis are well documented, but the optimal exercise dose remains unknown.To compare high-dose versus low-dose exercise therapy with regard to knee function, pain, and quality of life (QoL) in patients with long-term symptomatic knee osteoarthritis.A Swedish and Norwegian multicenter randomized controlled superiority trial with multiple follow-ups up to 12 months after the intervention. (ClinicalTrials.gov: NCT02024126).Primary health care facilities.189 patients with diagnosed knee osteoarthritis and a history of pain and decreased knee function were assigned to high-dose therapy (n = 98; 11 exercises; 70 to 90 minutes) or low-dose therapy (n = 91; 5 exercises; 20 to 30 minutes).Patient-tailored exercise programs according to the principles of medical exercise therapy. Global (aerobic), semiglobal (multisegmental), and local (joint-specific) exercises were performed 3 times a week for 12 weeks under supervision of a physiotherapist.The Knee Injury and Osteoarthritis Outcome Score (KOOS) was measured biweekly during the 3-month intervention period and at 6 and 12 months after the intervention. The primary end point was the mean difference in KOOS scores between groups at the end of the intervention (3 months). Secondary outcomes included pain intensity and QoL. The proportion of patients with minimal clinically important changes in primary and secondary outcomes was compared between groups.Both groups improved over time, but there were no benefits of high-dose therapy in most comparisons. One exception was the KOOS score for function in sports and recreation, where high-dose therapy was superior at the end of treatment and at 6-month follow-up. A small benefit in QoL at 6 and 12 months was also observed.There was no control group that did not exercise.The results do not support the superiority of high-dose exercise over low-dose exercise for most outcomes. However, small benefits with high-dose exercise were found for knee function in sports and recreation and for QoL.Swedish Rheumatic Fund.
Reply to Vanderpool <i>et al.</i>
Authors: Nils Kremer, Manuel Richter, Werner Seeger, Khodr Tello
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Reply to: The acute effects of prostacyclin on right ventricular contractility and pulmonary artery coupling." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp. –
Values and Preferences of Patients With Depressive Disorders Regarding Pharmacologic and Nonpharmacologic Treatments
Authors: Lisa Affengruber, Gernot Wagner, Andreea Dobrescu, Ana Toromanova, Andrea Chapman, Emma Persad, Irma Klerings, Gerald Gartlehner
Journal: Annals of Internal Medicine (2023)

Developers of clinical practice guidelines need to take patient values and preferences into consideration when weighing benefits and harms of treatment options for depressive disorder.To assess patient values and preferences regarding pharmacologic and nonpharmacologic treatments of depressive disorder.MEDLINE (Ovid) and PsycINFO (EBSCO) were searched for eligible studies published from 1 January 2014 to 30 November 2022.Pairs of reviewers independently screened 30% of search results. The remaining 70% of the abstracts were screened by single reviewers; excluded abstracts were checked by a second reviewer. Pairs of reviewers independently screened full texts.One reviewer extracted data and assessed the certainty of evidence, and a second reviewer checked for completeness and accuracy. Two reviewers independently assessed risk of bias.The review included 11 studies: 4 randomized controlled trials, 5 cross-sectional studies, and 2 qualitative studies. In 1 randomized controlled trial, participants reported at the start of therapy that they expected supportive-expressive psychotherapy and antidepressants to yield similar improvements. A cross-sectional study reported that non-Hispanic White participants and men generally preferred antidepressants over talk therapy, whereas Hispanic and non-Hispanic Black participants and women generally did not have a preference. Another cross-sectional study reported that the most important nonserious adverse events for patients treated with antidepressants were insomnia, anxiety, fatigue, weight gain, agitation, and sexual dysfunction. For other comparisons and outcomes, no conclusions could be drawn because of the insufficient certainty of evidence.The main limitation of this review is the low or insufficient certainty of evidence for most outcomes. No evidence was available on second-step depression treatment or differences in values and preferences based on gender, race/ethnicity, age, and depression severity.Low-certainty evidence suggests that there may be some differences in preferences for talk therapy or pharmacologic treatment of depressive disorders based on gender or race/ethnicity. In addition, low-certainty evidence suggests that insomnia, anxiety, fatigue, weight gain, agitation, and sexual dysfunction may be the most important nonserious adverse events for patients treated with antidepressants. Evidence is lacking or insufficient to draw any further conclusions about patients' weighing or valuation of the benefits and harms of depression treatments.American College of Physicians. (PROSPERO: CRD42020212442).
Cost-Effectiveness of First- and Second-Step Treatment Strategies for Major Depressive Disorder
Authors: Andreea Dobrescu, Andrea Chapman, Lisa Affengruber, Emma Persad, Ana Toromanova, Gernot Wagner, Irma Klerings, Robert Emprechtinger, Gerald Gartlehner
Journal: Annals of Internal Medicine (2023)

Major depressive disorder (MDD) is the most prevalent, disabling form of depression, with a high economic effect.To assess evidence on cost-effectiveness of pharmacologic and nonpharmacologic interventions as first- and second-step treatments in patients with MDD.Multiple electronic databases limited to English language were searched (1 January 2015 to 29 November 2022).Two investigators independently screened the literature. Seven economic modeling studies fulfilled the eligibility criteria.Data abstraction by a single investigator was confirmed by a second; 2 investigators independently rated risk of bias. One investigator determined certainty of evidence, and another checked for plausibility.Seven modeling studies met the eligibility criteria. In a U.S. setting over a 5-year time horizon, cognitive behavioral therapy (CBT) was cost-effective compared with second-generation antidepressants (SGAs) as a first-step treatment from the societal and health care sector perspectives. However, the certainty of evidence is low, and the findings should be interpreted cautiously. For second-step treatment, only switch strategies between SGAs were assessed. The evidence is insufficient to draw any conclusions.Methodologically heterogeneous studies, which compared only CBT and some SGAs, were included. No evidence on other psychotherapies or complementary and alternative treatments as first-step treatment or augmentation strategies as second-step treatment was available.Although CBT may be cost-effective compared with SGAs as a first-step treatment at a 5-year time horizon from the societal and health care sector perspectives, the certainty of evidence is low, and the findings need to be interpreted cautiously. For other comparisons, the evidence was entirely missing or insufficient to draw conclusions.American College of Physicians.
Associations of psychiatric disorders with sex chromosome aneuploidies in the Danish iPSYCH2015 dataset: a case-cohort study
Authors: Xabier Calle Sánchez, Simone Montalbano, Morteza Vaez, Morten Dybdahl Krebs, Jonas Byberg-Grauholm, Preben B Mortensen, Anders D Børglum, David M Hougaard, Merete Nordentoft, Daniel H Geschwind, Alfonso Buil, Andrew J Schork, Wesley K Thompson, Armin Raznahan, Dorte Helenius, Thomas Werge, Andrés Ingason
Journal: The Lancet Psychiatry (2023)
Radiofrequency induced heating of biodegradable orthopaedic screw implants during magnetic resonance imaging
Authors: Jonathan Espiritu, Mostafa Berangi, Hanna Cwieka, Kamila Iskhakova, Andre Kuehne, D.C. Florian Wieland, Berit Zeller-Plumhoff, Thoralf Niendorf, Regine Willumeit-Römer, Jan-Marten Seitz
Journal: Bioactive Materials (2023)

Magnesium (Mg)-based implants have re-emerged in orthopaedic surgery as an alternative to permanent implants. Literature reveals little information on how the degradation of biodegradable implants may introduce safety implications for patient follow-up using medical imaging. Magnetic resonance imaging (MRI) benefits post-surgery monitoring of bone healing and implantation sites. Previous studies demonstrated radiofrequency (RF) heating of permanent implants caused by electromagnetic fields used in MRI. Our investigation is the first to report the effect of the degradation layer on RF-induced heating of biodegradable orthopaedic implants. WE43 orthopaedic compression screws underwent
Tarlatamab, a First-in-Class DLL3-Targeted Bispecific T-Cell Engager, in Recurrent Small-Cell Lung Cancer: An Open-Label, Phase I Study
Authors: Luis Paz-Ares, Stephane Champiat, W. Victoria Lai, Hiroki Izumi, Ramaswamy Govindan, Michael Boyer, Horst-Dieter Hummel, Hossein Borghaei, Melissa L. Johnson, Neeltje Steeghs, Fiona Blackhall, Afshin Dowlati, Noemi Reguart, Tatsuya Yoshida, Kai He, Shirish M. Gadgeel, Enriqueta Felip, Yiran Zhang, Amrita Pati, Mukul Minocha, Sujoy Mukherjee, Amanda Goldrick, Dirk Nagorsen, Nooshin Hashemi Sadraei, Taofeek K. Owonikoko
Journal: Journal of Clinical Oncology (2023)

PURPOSE Small-cell lung cancer (SCLC) is an aggressive malignancy with limited treatments. Delta-like ligand 3 (DLL3) is aberrantly expressed in most SCLC. Tarlatamab (AMG 757), a bispecific T-cell engager molecule, binds both DLL3 and CD3 leading to T-cellb–mediated tumor lysis. Herein, we report phase I results of tarlatamab in patients with SCLC. PATIENTS AND METHODS This study evaluated tarlatamab in patients with relapsed/refractory SCLC. The primary end point was safety. Secondary end points included antitumor activity by modified RECIST 1.1, overall survival, and pharmacokinetics. RESULTS By July 19, 2022, 107 patients received tarlatamab in dose exploration (0.003 to 100 mg; n = 73) and expansion (100 mg; n = 34) cohorts. Median prior lines of anticancer therapy were 2 (range, 1-6); 49.5% received antiprogrammed death-1/programmed death ligand-1 therapy. Any-grade treatment-related adverse events occurred in 97 patients (90.7%) and grade b % 3 in 33 patients (30.8%). One patient (1%) had grade 5 pneumonitis. Cytokine release syndrome was the most common treatment-related adverse event, occurring in 56 patients (52%) including grade 3 in one patient (1%). Maximum tolerated dose was not reached. Objective response rate was 23.4% (95% CI, 15.7 to 32.5) including two complete and 23 partial responses. The median duration of response was 12.3 months (95% CI, 6.6 to 14.9). The disease control rate was 51.4% (95% CI, 41.5 to 61.2). The median progression-free survival and overall survival were 3.7 months (95% CI, 2.1 to 5.4) and 13.2 months (95% CI, 10.5 to not reached), respectively. Exploratory analysis suggests that selecting for increased DLL3 expression can result in increased clinical benefit. CONCLUSION In patients with heavily pretreated SCLC, tarlatamab demonstrated manageable safety with encouraging response durability. Further evaluation of this promising molecule is ongoing. [Media: see text]
Guideline for the Management of Fever and Neutropenia in Pediatric Patients With Cancer and Hematopoietic Cell Transplantation Recipients: 2023 Update
Authors: Thomas Lehrnbecher, Paula D. Robinson, Roland A. Ammann, Brian Fisher, Priya Patel, Robert Phillips, Melissa P. Beauchemin, Fabianne Carlesse, Elio Castagnola, Bonnie L. Davis, Caitlin W. Elgarten, Andreas H. Groll, Gabrielle M. Haeusler, Christa Koenig, Maria E. Santolaya, Wim J.E. Tissing, Joshua Wolf, Sarah Alexander, Helen Hu, L. Lee Dupuis, Lillian Sung
Journal: Journal of Clinical Oncology (2023)

To update a clinical practice guideline (CPG) for the empiric management of fever and neutropenia (FN) in pediatric patients with cancer and hematopoietic cell transplantation recipients.The International Pediatric Fever and Neutropenia Guideline Panel reconvened to conduct the second update of this CPG. We updated the previous systematic review to identify new randomized controlled trials (RCTs) evaluating any strategy for the management of FN in pediatric patients. Using the Grading of Recommendations Assessment, Development and Evaluation framework, evidence quality was classified as high, moderate, low, or very low. The panel updated recommendations related to initial management, ongoing management, and empiric antifungal therapy. Changes from the 2017 CPG were articulated, and good practice statements were considered.We identified 10 new RCTs in addition to the 69 RCTs identified in previous FN CPGs to inform the 2023 FN CPG. Changes from the 2017 CPG included two conditional recommendations regarding (1) discontinuation of empiric antibacterial therapy in clinically well and afebrile patients with low-risk FN if blood cultures remain negative at 48 hours despite no evidence of marrow recovery and (2) pre-emptive antifungal therapy for invasive fungal disease in high-risk patients not receiving antimold prophylaxis. The panel created a good practice statement to initiate FN CPG-consistent empiric antibacterial therapy as soon as possible in clinically unstable febrile patients.The updated FN CPG incorporates important modifications on the basis of recently published trials. Future work should focus on addressing knowledge gaps, improving CPG implementation, and measuring the impact of CPG-consistent care.
PD-1 blockade and CDK4/6 inhibition augment nonoverlapping features of T cell activation in cancer
Authors: Lestat R. Ali, Ana C. Garrido-Castro, Patrick J. Lenehan, Naima Bollenrucher, Courtney T. Stump, Michael Dougan, Shom Goel, Geoffrey I. Shapiro, Sara M. Tolaney, Stephanie K. Dougan
Journal: The Journal of Experimental Medicine (2023)

We performed single-cell RNA-sequencing and T cell receptor clonotype tracking of breast and ovarian cancer patients treated with the CDK4/6 inhibitor ribociclib and PD-1 blockade. We highlight evidence of two orthogonal treatment-associated phenomena: expansion of T cell effector populations and promotion of T cell memory formation. Augmentation of the antitumor memory pool by ribociclib boosts the efficacy of subsequent PD-1 blockade in mouse models of melanoma and breast cancer, pointing toward sequential therapy as a potentially safe and synergistic strategy in patients.
Nanovaccines Displaying the Influenza Virus Hemagglutinin in an Inverted Orientation Elicit an Enhanced Stalk‐Directed Antibody Response
Authors: Steven J. Frey, Juan Manuel Carreño, Dominika Bielak, Ammar Arsiwala, Clara G. Altomare, Chad Varner, Tania Rosen‐Cheriyan, Goran Bajic, Florian Krammer, Ravi S. Kane
Journal: Advanced Healthcare Materials (2023)

Despite the availability of licensed vaccines, influenza causes considerable morbidity and mortality worldwide. Current influenza vaccines elicit an immune response that primarily targets the head domain of the viral glycoprotein hemagglutinin (HA). Influenza viruses, however, readily evade this response by acquiring mutations in the head domain. While vaccines that target the more conserved HA stalk may circumvent this problem, low levels of antistalk antibodies are elicited by vaccination, possibly due to the poor accessibility of the stalk domain to B cell receptors. In this work, it is demonstrated that nanoparticles presenting HA in an inverted orientation generate tenfold higher antistalk antibody titers after a prime immunization and fivefold higher antistalk titers after a boost than nanoparticles displaying HA in its regular orientation. Moreover, nanoparticles presenting HA in an inverted orientation elicit a broader antistalk response that reduces mouse weight loss and improves survival after challenge to a greater extent than nanoparticles displaying HA in a regular orientation. Refocusing the antibody response toward conserved epitopes by controlling antigen orientation may enable the design of broadly protective nanovaccines targeting influenza viruses and other pathogens with pandemic potential.
COVID-19 Vaccination During Pregnancy
Authors: Song Mao
Journal: JAMA Pediatrics (2023)

Atsuyuki Watanabe, MD; Jun Yasuhara, MD; Masao Iwagami, MD, PhD; Yoshihisa Miyamoto, MD; Yuji Yamada, MD; Yukio Suzuki, MD, PhD; Hisato Takagi, MD, PhD; Toshiki Kuno, MD, PhD
Gut microbiota biofilms: From regulatory mechanisms to therapeutic targets
Authors: Andre G. Buret, Thibault Allain
Journal: The Journal of Experimental Medicine (2023)

Gut microbiota contain communities of viruses, bacteria, fungi, and Eukarya, and live as biofilms. In health, these biofilms adhere to the intestinal mucus surface without contacting the epithelium. Disruptions to the equilibrium between these biofilms and the host may create invasive pathobionts from these commensal communities and contribute to disease pathogenesis. Environmental factors appear to dominate over genetics in determining the shifts in microbiota populations and function, including when comparing microbiota between low-income and industrialized countries. The observations discussed herein carry enormous potential for the development of novel therapies targeting phenotype in microbiota dysbiosis.
Trends in FDA Adverse Events Reporting for Inferior Vena Cava Filters and Estimated Insertions in the US, 2016 to 2020
Authors: Rachel E. Warren, Sanket S. Dhruva, Madris Kinard, John M. Neuhaus, Rita F. Redberg
Journal: JAMA Internal Medicine (2023)

This quality improvement study identifies adverse events for inferior vena cava filters and reports changes in adverse event reporting and estimated insertions between 2016 and 2020 in the US.
Systematic in vitro and in vivo study on biodegradable binary Zn-0.2 at% Rare Earth alloys (Zn-RE: Sc, Y, La–Nd, Sm–Lu)
Authors: Shaokang Du, Yunong Shen, Yufeng Zheng, Yan Cheng, Xiaoxue Xu, Dafu Chen, Dandan Xia
Journal: Bioactive Materials (2023)

Biomedical implants and devices for tissue engineering in clinics, mainly made of polymers and stiff metallic materials, require possibly secondary surgery or life-long medicine. Biodegradable metals for biomedical implants and devices exhibit huge potential to improve the prognosis of patients. In this work, we developed a new type of biodegradable binary zinc (Zn) alloys with 16 rare earth elements (REEs) including Sc, Y, La to Nd, and Sm to Lu, respectively. The effects of REEs on the alloy microstructure, mechanical properties, corrosion behavior and in vitro and in vivo biocompatibility of Zn were systematically investigated using pure Zn as control. All Zn-RE alloys generally exhibited improved mechanical properties, and biocompatibilities compared to pure Zn, especially the tensile strength and ductility of Zn-RE alloys were dramatically enhanced. Among the Zn-RE alloys, different REEs presented enhancement effects at varied extent. Y, Ho and Lu were the three elements displaying greatest improvements in majority of alloys properties, while Eu, Gd and Dy exhibited least improvement. Furthermore, the Zn-RE alloys were comparable with other Zn alloys and also exhibited superior properties to Mg-RE alloys. The in vivo experiment using Zn-La, Zn-Ce, and Zn-Nd alloys as tibia bone implants in rabbit demonstrated the excellent tissue biocompatibility and much more obvious osseointegration than the pure Zn control group. This work presented the significant potential of the developed Zn-RE binary alloys as novel degradable metal for biomedical implants and devices.
ADAR1 Non-Editing Function in Macrophage Activation and Abdominal Aortic Aneurysm
Authors: Dunpeng Cai, Chenming Sun, Takashi Murashita, Xingyi Que, Shi-You Chen
Journal: Circulation Research (2023)

Macrophage activation plays a critical role in abdominal aortic aneurysm (AAA) development. However, molecular mechanisms controlling macrophage activation and vascular inflammation in AAA remain largely unknown. The objective of the study was to identify novel mechanisms underlying adenosine deaminase acting on RNA (ADAR1) function in macrophage activation and AAA formation.
Community-acquired Staphylococcus aureus meningitis in adults
Authors: Thijs M. van Soest, Maria Birgitte Søndermølle, Matthijs C. Brouwer, Nora Chekrouni, Anders Rhod Larsen, Andreas Petersen, Nina M. van Sorge, Henrik Nielsen, Diederik van de Beek, Jacob Bodilsen, Christian Østergaard Andersen, Jacob  Bodilsen, Birgitte Rønde Hansen, Jannik Helweg-Larsen, Micha Jepsen, Lykke Larsen, Hans Rudolf Lüttichau, Henrik Nielsen, Merete Storgaard, Lothar Wiese
Journal: Journal of Infection (2023)
Cerebral Amyloid Angiopathy—How to Translate Updated Diagnostic Criteria for This Multifaceted Disorder to Clinical Practice?
Authors: Geert Jan Biessels, Ana Sofia Costa
Journal: JAMA Neurology (2023)

This Viewpoint discusses recent efforts to update diagnostic criteria for cerebral amyloid angiopathy as well as questions and challenges in counseling patients about prognosis and deciding on optimal treatment.
Risk prediction models for endometrial cancer: development and validation in an international consortium
Authors: Joy Shi, Peter Kraft, Bernard A Rosner, Yolanda Benavente, Amanda Black, Louise A Brinton, Chu Chen, Megan A Clarke, Linda S Cook, Laura Costas, Luigino Dal Maso, Jo L Freudenheim, Jon Frias-Gomez, Christine M Friedenreich, Montserrat Garcia-Closas, Marc T Goodman, Lisa Johnson, Carlo La Vecchia, Fabio Levi, Jolanta Lissowska, Lingeng Lu, Susan E McCann, Kirsten B Moysich, Eva Negri, Kelli O'Connell, Fabio Parazzini, Stacey Petruzella, Jerry Polesel, Jeanette Ponte, Timothy R Rebbeck, Peggy Reynolds, Fulvio Ricceri, Harvey A Risch, Carlotta Sacerdote, Veronica W Setiawan, Xiao-Ou Shu, Amanda B Spurdle, Britton Trabert, Penelope M Webb, Nicolas Wentzensen, Lynne R Wilkens, Wang Hong Xu, Hannah P Yang, Herbert Yu, Mengmeng Du, Immaculata De Vivo
Journal: JNCI Journal of the National Cancer Institute (2023)

Abstract Background Endometrial cancer risk stratification may help target interventions, screening, or prophylactic hysterectomy to mitigate the rising burden of this cancer. However, existing prediction models have been developed in select cohorts and have not considered genetic factors. Methods We developed endometrial cancer risk prediction models using data on postmenopausal White women aged 45-85 years from 19 case-control studies in the Epidemiology of Endometrial Cancer Consortium (E2C2). Relative risk estimates for predictors were combined with age-specific endometrial cancer incidence rates and estimates for the underlying risk factor distribution. We externally validated the models in 3 cohorts: Nurses’ Health Study (NHS), NHS II, and the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Results Area under the receiver operating characteristic curves for the epidemiologic model ranged from 0.64 (95% confidence interval [CI] = 0.62 to 0.67) to 0.69 (95% CI = 0.66 to 0.72). Improvements in discrimination from the addition of genetic factors were modest (no change in area under the receiver operating characteristic curves in NHS; PLCO = 0.64 to 0.66). The epidemiologic model was well calibrated in NHS II (overall expected-to-observed ratio [E/O] = 1.09, 95% CI = 0.98 to 1.22) and PLCO (overall E/O = 1.04, 95% CI = 0.95 to 1.13) but poorly calibrated in NHS (overall E/O = 0.55, 95% CI = 0.51 to 0.59). Conclusions Using data from the largest, most heterogeneous study population to date (to our knowledge), prediction models based on epidemiologic factors alone successfully identified women at high risk of endometrial cancer. Genetic factors offered limited improvements in discrimination. Further work is needed to refine this tool for clinical or public health practice and expand these models to multiethnic populations.